Histone‐Deacetylase‐Targeted Fluorescent Ruthenium(II) Polypyridyl Complexes as Potent Anticancer Agents |
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Authors: | Rui‐Rong Ye Dr Zhuo‐Feng Ke Dr Cai‐Ping Tan Liang He Prof Liang‐Nian Ji Prof?Dr Zong‐Wan Mao |
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Institution: | MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat‐sen University, Guangzhou 510275 (P. R. China), Fax: (+86)?20‐8411‐2245 |
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Abstract: | Histone deacetylases inhibitors (HDACis) have gained much attention as a new class of anticancer agents in recent years. Herein, we report a series of fluorescent ruthenium(II) complexes containing N1‐hydroxy‐N8‐(1,10‐phenanthrolin‐5‐yl)octanediamide ( L ), a suberoylanilide hydroxamic acid (SAHA) derivative, as a ligand. As expected, these complexes show interesting chemiphysical properties, including relatively high quantum yields, large Stokes shifts, and long emission lifetimes. The in vitro inhibitory effect of the most effective drug, Ru(DIP)2 L ](PF6)2 ( 3 ; DIP: 4,7‐diphenyl‐1,10‐phenanthroline), on histone deacetylases (HDACs) is approximately equivalent in activity to that of SAHA, and treatment with complex 3 results in increased levels of the acetylated histone H3. Complex 3 is highly active against a panel of human cancer cell lines, whereas it shows relatively much lower toxicity to normal cells. Further mechanism studies show that complex 3 can elicit cell cycle arrest and induce apoptosis through mitochondria‐related pathways and the production of reactive oxygen species. These data suggest that these fluorescent ruthenium(II)–HDACi conjugates may represent a promising class of anticancer agents for potential dual imaging and therapeutic applications targeting HDACs. |
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Keywords: | antitumor agents apoptosis enzymes inhibitors ruthenium |
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